DOI

10.17077/etd.0nm0-y0tq

Document Type

Dissertation

Date of Degree

Fall 2018

Degree Name

PhD (Doctor of Philosophy)

Degree In

Neuroscience

First Advisor

Narayanan, Nandakumar

First Committee Member

Blumberg, Mark

Second Committee Member

Kamholz, John

Third Committee Member

Tranel, Daniel

Fourth Committee Member

Wasserman, Edward

Abstract

The ability to take in one’s environment, integrate relevant information, and then act appropriately is an incredibly complex feat that organisms do continuously. Disruption in the ability to think and act clearly, or cognitive dysfunction, is a debilitating aspect of neuropsychiatric diseases like schizophrenia. The prefrontal cortex and the striatum are key brain regions for functional and dysfunctional cognition, but the way that they interact to allow for cognitive processing is poorly understood.

To get at these questions, I manipulated and recorded from medial frontal and striatal neurons—frontostriatal ensembles—while rats engaged in interval timing, an elementary cognitive function that engages both areas. I report four main results. First, ramping activity—a gradual, consistent change in neuronal firing rate across time—is observed throughout frontostriatal ensembles. Secondly, medial frontal areas dynamically reflect changing temporal conditions during learning and precede these same changes in striatal areas. Thirdly, interval timing and striatal ramping activity are disrupted when the medial frontal cortex is inactivated. Finally, this behavioral impairment can be reduced by optogenetic stimulation of frontostriatal terminals.

My results support the view that striatal neurons integrate medial frontal activity and suggest a possible mechanism—ramping activity—through which neurons might represent the passage of time. These observations elucidate temporal processing in frontostriatal circuits and provide insight into how the medial frontal cortex exerts top-down control of cognitive processing in the striatum. My hope is that these findings will contribute to a clearer understanding of basic cognitive processing and might inform future approaches to treatments that address cognitive dysfunction.

Keywords

behavior, electrophysiology, interval timing, optogenetics, prefrontal cortex, striatum

Pages

xiii, 154 pages

Bibliography

Includes bibliographical references (pages 138-154).

Comments

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Copyright

Copyright © 2018 Eric Blockhus Emmons

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